In this New Digest:
- Summaries of two studies being published online November 2, 2009, in the Journal of Clinical Oncologyshowing that women with small, HER2-positive breast cancers that had not spread to the lymph nodes had an elevated risk of recurrence and metastasis compared with women with small HER2-negative node-negative breast cancers.
- Quote for attribution from Jennifer Obel, MD, American Society of Clinical Oncology breast cancer expert
- Links to additional information on Cancer.Net, ASCO’s patient Web site
Two retrospective studies led by researchers in the United States and Italy report that women with HER2-positive breast cancers 1 cm or less in diameter that have not spread to the lymph nodes (“node-negative” tumors) have a risk of recurrence that is two to five times greater than that of women with HER2-negative breast cancers. The U.S. study also identified an increased risk of metastasis among women with small HER2-positive tumors, compared to those with HER2-negative tumors.
HER2-positive disease (in which tumors over-express the HER2 protein) is relatively uncommon in women with small, early-stage breast cancers, accounting for approximately 7 to 10 percent of the cases in these two studies. Women with small HER2-positive tumors are currently treated with lumpectomy followed by radiation. Some 25 percent of all breast cancers over-express the HER2 protein, which is known to be associated with a higher risk of recurrence and worse overall survival. In the U.S., trastuzumab is FDA-approved for the treatment of HER2-positive, node-positive disease and for women with node-negative disease with hormone (estrogen or progesterone) receptor-positive tumors who have another high-risk feature. Consensus guidelines, such as those from the National Comprehensive Cancer Network, currently do not recommend trastuzumab therapy for tumors less than 1 cm, due to a lack of prior supporting evidence.
Given these findings, the authors of both new JCO studies recommended that adjuvant anti-HER2 therapy with trastuzumab (Herceptin) be considered for patients with small, HER2-positive tumors. In an accompanying editorial, Harold J. Burstein, MD, PhD, and Eric P. Winer, MD, of Dana-Farber Cancer Institute and Brigham & Women’s Hospital, explained, “For the 15 to 20 percent of patients with HER2 over-expressing tumors, the success of trastuzumab has fast-forwarded our efforts and has led to a dramatic improvement in clinical outcomes.” Drs. Winer and Burstein added that while they agree that trastuzumab should be considered in this setting, additional therapy should generally be limited to patients with tumors 0.5 cm or larger and that abbreviated courses of adjuvant treatment be considered to minimize the risk of side effects.
U.S. study finds that HER2 status strongly predicts risk of breast cancer recurrence, metastasis
Researchers from M. D. Anderson Cancer Center in Houston reported that women with HER2-positive breast cancers 1 cm or less in diameter that have not spread to the lymph nodes have nearly three times the risk of recurrence and more than five times the risk of metastasis five years after diagnosis compared with women with similar-sized HER2-negative tumors.
“We expected the risk of recurrence and metastasis in HER2-positive node-negative patients with small tumors to be higher than in women with HER2-negative tumors, but we didn’t expect the magnitude of this risk to be so high,” said lead author Ana M. Gonzalez-Angulo, MD, associate professor in the Department of Breast Medical Oncology at the University of Texas M. D. Anderson Cancer Center. “This elevated risk is unacceptable, and indicates that women with small HER2-positive node-negative breast tumors should be offered participation in clinical trials assessing anti-HER2 therapies, such as trastuzumab [Herceptin], or other adjuvant treatment.”
Dr. Gonzalez-Angulo and her colleagues reviewed records from 965 women diagnosed between 1990 and 2002 at their institution with breast cancers 1 cm or less in size that had not spread to nearby lymph nodes. They compared the rates of recurrence and metastasis among women with HER2-positive and HER2-negative breast cancers after a median follow-up of six years. In addition, samples from an additional 350 women with breast cancer from two other institutions were analyzed to validate their findings.
The investigators found that five years after diagnosis, 77.1 percent of the HER2-positive patients were free of recurrence and 86.4 percent were free of metastasis, compared with 93.7 percent and 97.2 percent of the HER2-negative patients, respectively. Compared with women who had HER2-negative tumors, women with HER2-positive tumors were 2.68 times more likely to experience a recurrence and 5.3 times more likely to experience metastasis. The results of the analysis of the breast cancers from other institutions were consistent with these findings.
“High Risk of Recurrence for Patients With Breast Cancer Who Have Human Epidermal Growth Factor Receptor 2–Positive, Node-Negative Tumors 1 cm or Smaller,” Gonzalez-Angulo, A., et. al. University of Texas M. D. Anderson Cancer Center, Houston, TX.
Italian study reports small HER2-positive breast tumors have higher risk of recurrence, and poorer disease-free survival
In the second study, researchers from the Istituto Europeo di Oncologia in Milan found that women with HER2-positive node-negative breast tumors 1 cm or less in diameter have a 2.4-fold greater risk of recurrence compared to those with HER2-negative disease. Additionally, women with HER2-positive tumors that also contained receptors for progesterone and/or estrogen had worse disease-free survival than women with hormone-receptor positive, HER2-negative tumors.
“Advances in screening have helped us to increasingly identify small, earlier stage breast tumors, but there is little clear-cut guidance on how these tumors can be treated most effectively,” said lead author Giuseppe Curigliano, MD, PhD, senior deputy director of the Division of Medical Oncology at the Istituto Europeo di Oncologia. “And while there are no definitive data that support treatment with trastuzumab for patients with small, HER2-positive breast tumors that have not spread to the lymph nodes, the option should be discussed with patients.”
Dr. Curigliano and his colleagues reviewed records from 2,130 women who were surgically treated at their institution between 1999 and 2006 for tumors 1 cm or less in diameter that had not spread to the lymph nodes. Of these women, 150 (7 percent) had HER2-positive disease. Researchers examined the risk of recurrence and disease-free survival among women with both HER2-positive and HER2-negative disease, and further stratified patients according to hormone receptor status (the presence or absence of receptors for estrogen or progesterone).
After a median follow-up of 4.6 years, they found that HER2-positive disease was associated with less favorable disease-free survival, regardless of hormone receptor status. Among women with hormone receptor positive disease, 5-year disease-free survival was 92 percent for patients with HER2-positive tumors and 99 percent for patients with HER2-negative tumors. In patients with hormone receptor-negative disease, disease-free survival was 91 percent and 92 percent, respectively.
“Clinical Relevance of HER2 Overexpression/Amplification in Patients With Small Tumor Size and Node-Negative Breast Cancer,” Curigliano G., et. al. Istituto Europeo di Oncologia, Milan, Italy.
Jennifer Obel, MD, ASCO breast cancer expert and Cancer Communications Committee member
“Advances in screening have enabled the detection of breast cancers at an earlier, and generally more treatable stage. Physicians are often challenged with finding a balance between aggressive treatment and overtreatment, as we don’t want to subject patients to the side effects and costs of unnecessary therapy.”
“Trastuzumab significantly improves outcome for high risk, early stage, HER2-positive breast cancer patients. The landmark studies of trastuzumab in early stage breast cancer generally included patients with either larger sized tumors or lymph node involvement and they found that chemotherapy and trastuzumab dramatically reduced the risk of breast cancer recurrence by more than 50%. But, what we have not grasped is the risk of recurrence for smaller HER2 positive tumors. We now know that even women with HER2 positive tumors less than 1 cm face a substantial risk of recurrence, which approaches almost 25% at five years. Trastuzumab is an extremely effective targeted agent, and patients and physicians should discuss its use in women with these smaller tumors.”
Multimedia Video: Eric Winer, MD, discusses both studies and editorial
Relevant Links on Cancer.Net
The Journal of Clinical Oncology is the tri-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world’s leading professional society representing physicians who treat people with cancer.
ATTRIBUTION TO THE JOURNAL OF CLINICAL ONCOLOGY IS REQUESTED IN ALL NEWS COVERAGE.
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